REACTIVITY OF MESENTERIC-ARTERIES FROM FRUCTOSE HYPERTENSIVE RATS TO ENDOTHELIN-1

We previously demonstrated that mesenteric arteries from hyperinsuline mic, insulin resistant fructose hypertensive (FH) rats contain a highe r absolute amount of ET-1 and exhibit defective endothelium-dependent vasodilation. Furthermore, chronic ET receptor blockade with bosentan completely prevented the rise in blood pressure in these rats. The pre sent study was undertaken to examine 1) whether the reactivity of mese nteric arteries to ET-1 is altered in FH rats, and 2) whether chronic bosentan treatment has any effect on ET-1 responsiveness and endotheli um-dependent vasodilation. Male Sprague Dawley rats were divided into four groups: control (C), control bosentan-treated (CB), fructose (F) and fructose bosentan-treated (FB). Chronic oral bosentan treatment (1 00 mg/kg/day) was initiated in the CB and FB groups 1 week prior to in itiating the fructose diet. At week 16, the F group was hyperinsulinem ic and hypertensive when compared to the C group (plasma insulin: 5.8 +/- 0.3 v C 3.2 +/- 0.5 ng/mL, P <.001; systolic BP: 157 +/- 5 v C 130 +/- 4 mm Hg, P <.001). Treatment of the F group with bosentan prevent ed the rise in BP (FB: 133 +/- 3 mm Hg; P <.001 v Fl. Analysis of the pressurized mesenteric resistance arterioles demonstrated that the wal l thickness as expressed as percentage of internal diameter did not di ffer between arteries from C and F rats, when measured over a range of transmural pressures. Constrictor responses of resistance arterioles to NE were similar for C and F rats when studied at transmural pressur es of either 120 mm Hg or 160 mm Hg, respectively. The maximum contrac tile response and the sensitivity of superior mesenteric arteries to N E did not differ between the groups, either with or without the endoth elium. However, the maximum contractile response to ET-1 was depressed in the F group both with (+) and without (-) the endothelium [(+): 1. 50 +/- 0.11 v C 1.88 +/- 0.1 g/mm(3), P <.05, (-): 1.68 +/- 0.11 v C 2 .05 +/- 0.1 g/mm(3), P <.05.]. Furthermore, the endothelium intact F a rteries exhibited a decreased sensitivity to ET-1 (pD(2) values F 8.36 +/- 0.11 v C 8.83 +/- 0.07). Chronic bosentan treatment of the F grou p restored the maximum tension responses of arteries to ET-1 [(+) in t he FB group: 1.88 +/- 0.12 g/mm(3) v C, P >.05, (-): 1.95 +/- 0.05 g/m m(3) v C, P >.05] but had no effect on the responses of the CB group. In arteries with intact: endothelium, bosentan treatment restored the sensitivity of the F arteries to ET-1 (pD(2) values FB 8.82 +/- 0.05 v C, P <.05). Endothelium-dependent relaxation responses were diminishe d in the F group, which were unaffected by bosentan treatment. These d ata suggest that mesenteric arteries from FH demonstrate a specific al teration towards the reactivity to ET-1, which is restored by long-ter m bosentan treatment. (C) 1997 American Journal of Hypertension, Ltd.